R Under development (unstable) (2024-08-23 r87049 ucrt) -- "Unsuffered Consequences" Copyright (C) 2024 The R Foundation for Statistical Computing Platform: x86_64-w64-mingw32/x64 R is free software and comes with ABSOLUTELY NO WARRANTY. You are welcome to redistribute it under certain conditions. Type 'license()' or 'licence()' for distribution details. R is a collaborative project with many contributors. Type 'contributors()' for more information and 'citation()' on how to cite R or R packages in publications. Type 'demo()' for some demos, 'help()' for on-line help, or 'help.start()' for an HTML browser interface to help. Type 'q()' to quit R. > # R CMD BATCH --no-timing --no-restore --no-save pbtk_test.R pbtk_test.Rout > > # Get rid of anything in the workspace: > rm(list=ls()) > > library(httk) > > calc_analytic_css(chem.name="bisphenol a",model="pbtk") Plasma concentration returned in uM units. [1] 0.9417 Warning messages: 1: In get_clint(dtxsid = dtxsid, chem.name = chem.name, chem.cas = chem.cas, : Clint is provided as a distribution. 2: In apply_clint_adjustment(Clint.point, Fu_hep = Fu_hep, suppress.messages = suppress.messages) : Clint adjusted for in vitro partitioning (Kilford, 2008), see calc_hep_fu. 3: In get_fup(dtxsid = dtxsid, chem.name = chem.name, chem.cas = chem.cas, : Fraction unbound is provided as a distribution. 4: In apply_fup_adjustment(fup.point, fup.correction = fup.adjustment, : Fup adjusted for in vivo lipid partitioning (Pearce, 2017), see calc_fup_correction. 5: In available_rblood2plasma(chem.cas = chem.cas, species = species, : Human in vivo measured Rblood2plasma used. 6: In get_caco2(chem.cas = chem.cas, chem.name = chem.name, dtxsid = dtxsid, : Default value of 1.6 used for Caco2 permeability. > calc_analytic_css(chem.cas="80-05-7",model="pbtk") Plasma concentration returned in uM units. [1] 0.9417 Warning messages: 1: In get_clint(dtxsid = dtxsid, chem.name = chem.name, chem.cas = chem.cas, : Clint is provided as a distribution. 2: In apply_clint_adjustment(Clint.point, Fu_hep = Fu_hep, suppress.messages = suppress.messages) : Clint adjusted for in vitro partitioning (Kilford, 2008), see calc_hep_fu. 3: In get_fup(dtxsid = dtxsid, chem.name = chem.name, chem.cas = chem.cas, : Fraction unbound is provided as a distribution. 4: In apply_fup_adjustment(fup.point, fup.correction = fup.adjustment, : Fup adjusted for in vivo lipid partitioning (Pearce, 2017), see calc_fup_correction. 5: In available_rblood2plasma(chem.cas = chem.cas, species = species, : Human in vivo measured Rblood2plasma used. 6: In get_caco2(chem.cas = chem.cas, chem.name = chem.name, dtxsid = dtxsid, : Default value of 1.6 used for Caco2 permeability. > calc_analytic_css(parameters=parameterize_pbtk(chem.cas="80-05-7"),model="pbtk") Plasma concentration returned in uM units. [1] 0.9417 Warning messages: 1: In get_clint(dtxsid = dtxsid, chem.name = chem.name, chem.cas = chem.cas, : Clint is provided as a distribution. 2: In apply_clint_adjustment(Clint.point, Fu_hep = Fu_hep, suppress.messages = suppress.messages) : Clint adjusted for in vitro partitioning (Kilford, 2008), see calc_hep_fu. 3: In get_fup(dtxsid = dtxsid, chem.name = chem.name, chem.cas = chem.cas, : Fraction unbound is provided as a distribution. 4: In apply_fup_adjustment(fup.point, fup.correction = fup.adjustment, : Fup adjusted for in vivo lipid partitioning (Pearce, 2017), see calc_fup_correction. 5: In available_rblood2plasma(chem.cas = chem.cas, species = species, : Human in vivo measured Rblood2plasma used. 6: In get_caco2(chem.cas = chem.cas, chem.name = chem.name, dtxsid = dtxsid, : Default value of 1.6 used for Caco2 permeability. > calc_analytic_css(chem.name="bisphenol a",model="pbtk",tissue="liver") Plasma concentration for liver returned in uM units. [1] 20.58 Warning messages: 1: In get_clint(dtxsid = dtxsid, chem.name = chem.name, chem.cas = chem.cas, : Clint is provided as a distribution. 2: In apply_clint_adjustment(Clint.point, Fu_hep = Fu_hep, suppress.messages = suppress.messages) : Clint adjusted for in vitro partitioning (Kilford, 2008), see calc_hep_fu. 3: In get_fup(dtxsid = dtxsid, chem.name = chem.name, chem.cas = chem.cas, : Fraction unbound is provided as a distribution. 4: In apply_fup_adjustment(fup.point, fup.correction = fup.adjustment, : Fup adjusted for in vivo lipid partitioning (Pearce, 2017), see calc_fup_correction. 5: In available_rblood2plasma(chem.cas = chem.cas, species = species, : Human in vivo measured Rblood2plasma used. 6: In get_caco2(chem.cas = chem.cas, chem.name = chem.name, dtxsid = dtxsid, : Default value of 1.6 used for Caco2 permeability. > calc_analytic_css(chem.name="bisphenol a",model="pbtk",tissue="brain") Plasma concentration for brain returned in uM units. [1] 5.496 Warning messages: 1: In get_clint(dtxsid = dtxsid, chem.name = chem.name, chem.cas = chem.cas, : Clint is provided as a distribution. 2: In apply_clint_adjustment(Clint.point, Fu_hep = Fu_hep, suppress.messages = suppress.messages) : Clint adjusted for in vitro partitioning (Kilford, 2008), see calc_hep_fu. 3: In get_fup(dtxsid = dtxsid, chem.name = chem.name, chem.cas = chem.cas, : Fraction unbound is provided as a distribution. 4: In apply_fup_adjustment(fup.point, fup.correction = fup.adjustment, : Fup adjusted for in vivo lipid partitioning (Pearce, 2017), see calc_fup_correction. 5: In available_rblood2plasma(chem.cas = chem.cas, species = species, : Human in vivo measured Rblood2plasma used. 6: In get_caco2(chem.cas = chem.cas, chem.name = chem.name, dtxsid = dtxsid, : Default value of 1.6 used for Caco2 permeability. > > head(solve_pbtk(chem.name="bisphenol a",days=1)) None of the monitored components undergo unit conversions (i.e. conversion factor of 1). AUC is area under the plasma concentration curve in uM*days units with Rblood2plasma = 0.795. The model outputs are provided in the following units: umol: Agutlumen, Atubules, Ametabolized uM: Cgut, Cliver, Cven, Clung, Cart, Crest, Ckidney, Cplasma uM*days: AUC time Agutlumen Cgut Cliver Cven Clung Cart [1,] 0.00000000 197.5 0.0000 0.000e+00 0.000e+00 0.000e+00 0.000e+00 [2,] 0.00010000 197.3 0.1582 4.792e-04 5.620e-07 3.220e-07 2.000e-09 [3,] 0.01041667 180.0 10.1400 3.070e+00 3.649e-02 2.976e-01 3.140e-02 [4,] 0.02083333 164.0 13.6300 7.610e+00 1.027e-01 8.865e-01 9.700e-02 [5,] 0.03125000 149.5 14.7600 1.113e+01 1.622e-01 1.425e+00 1.576e-01 [6,] 0.04166667 136.3 14.9800 1.339e+01 2.072e-01 1.834e+00 2.038e-01 Crest Ckidney Cplasma Atubules Ametabolized AUC [1,] 0.000000 0.0000 0.000e+00 0.0000000 0.000e+00 0.0000000 [2,] 0.000000 0.0000 7.060e-07 0.0000000 5.000e-09 0.0000000 [3,] 0.008015 0.3847 4.590e-02 0.0005859 3.316e-03 0.0001704 [4,] 0.056450 1.7590 1.292e-01 0.0042390 1.856e-02 0.0010780 [5,] 0.150100 3.2970 2.041e-01 0.0116100 4.541e-02 0.0028280 [6,] 0.276300 4.5580 2.606e-01 0.0220600 8.041e-02 0.0052650 Warning messages: 1: In get_clint(dtxsid = dtxsid, chem.name = chem.name, chem.cas = chem.cas, : Clint is provided as a distribution. 2: In apply_clint_adjustment(Clint.point, Fu_hep = Fu_hep, suppress.messages = suppress.messages) : Clint adjusted for in vitro partitioning (Kilford, 2008), see calc_hep_fu. 3: In get_fup(dtxsid = dtxsid, chem.name = chem.name, chem.cas = chem.cas, : Fraction unbound is provided as a distribution. 4: In apply_fup_adjustment(fup.point, fup.correction = fup.adjustment, : Fup adjusted for in vivo lipid partitioning (Pearce, 2017), see calc_fup_correction. 5: In available_rblood2plasma(chem.cas = chem.cas, species = species, : Human in vivo measured Rblood2plasma used. 6: In get_caco2(chem.cas = chem.cas, chem.name = chem.name, dtxsid = dtxsid, : Default value of 1.6 used for Caco2 permeability. > head(solve_pbtk(chem.cas="80-05-7",days=1)) None of the monitored components undergo unit conversions (i.e. conversion factor of 1). AUC is area under the plasma concentration curve in uM*days units with Rblood2plasma = 0.795. The model outputs are provided in the following units: umol: Agutlumen, Atubules, Ametabolized uM: Cgut, Cliver, Cven, Clung, Cart, Crest, Ckidney, Cplasma uM*days: AUC time Agutlumen Cgut Cliver Cven Clung Cart [1,] 0.00000000 197.5 0.0000 0.000e+00 0.000e+00 0.000e+00 0.000e+00 [2,] 0.00010000 197.3 0.1582 4.792e-04 5.620e-07 3.220e-07 2.000e-09 [3,] 0.01041667 180.0 10.1400 3.070e+00 3.649e-02 2.976e-01 3.140e-02 [4,] 0.02083333 164.0 13.6300 7.610e+00 1.027e-01 8.865e-01 9.700e-02 [5,] 0.03125000 149.5 14.7600 1.113e+01 1.622e-01 1.425e+00 1.576e-01 [6,] 0.04166667 136.3 14.9800 1.339e+01 2.072e-01 1.834e+00 2.038e-01 Crest Ckidney Cplasma Atubules Ametabolized AUC [1,] 0.000000 0.0000 0.000e+00 0.0000000 0.000e+00 0.0000000 [2,] 0.000000 0.0000 7.060e-07 0.0000000 5.000e-09 0.0000000 [3,] 0.008015 0.3847 4.590e-02 0.0005859 3.316e-03 0.0001704 [4,] 0.056450 1.7590 1.292e-01 0.0042390 1.856e-02 0.0010780 [5,] 0.150100 3.2970 2.041e-01 0.0116100 4.541e-02 0.0028280 [6,] 0.276300 4.5580 2.606e-01 0.0220600 8.041e-02 0.0052650 Warning messages: 1: In get_clint(dtxsid = dtxsid, chem.name = chem.name, chem.cas = chem.cas, : Clint is provided as a distribution. 2: In apply_clint_adjustment(Clint.point, Fu_hep = Fu_hep, suppress.messages = suppress.messages) : Clint adjusted for in vitro partitioning (Kilford, 2008), see calc_hep_fu. 3: In get_fup(dtxsid = dtxsid, chem.name = chem.name, chem.cas = chem.cas, : Fraction unbound is provided as a distribution. 4: In apply_fup_adjustment(fup.point, fup.correction = fup.adjustment, : Fup adjusted for in vivo lipid partitioning (Pearce, 2017), see calc_fup_correction. 5: In available_rblood2plasma(chem.cas = chem.cas, species = species, : Human in vivo measured Rblood2plasma used. 6: In get_caco2(chem.cas = chem.cas, chem.name = chem.name, dtxsid = dtxsid, : Default value of 1.6 used for Caco2 permeability. > head(solve_pbtk(parameters=parameterize_pbtk(chem.cas="80-05-7"),days=1)) None of the monitored components undergo unit conversions (i.e. conversion factor of 1). AUC is area under the plasma concentration curve in uM*days units with Rblood2plasma = 0.795. The model outputs are provided in the following units: umol: Agutlumen, Atubules, Ametabolized uM: Cgut, Cliver, Cven, Clung, Cart, Crest, Ckidney, Cplasma uM*days: AUC time Agutlumen Cgut Cliver Cven Clung Cart [1,] 0.00000000 197.5 0.0000 0.000e+00 0.000e+00 0.000e+00 0.000e+00 [2,] 0.00010000 197.3 0.1582 4.792e-04 5.620e-07 3.220e-07 2.000e-09 [3,] 0.01041667 180.0 10.1400 3.070e+00 3.649e-02 2.976e-01 3.140e-02 [4,] 0.02083333 164.0 13.6300 7.610e+00 1.027e-01 8.865e-01 9.700e-02 [5,] 0.03125000 149.5 14.7600 1.113e+01 1.622e-01 1.425e+00 1.576e-01 [6,] 0.04166667 136.3 14.9800 1.339e+01 2.072e-01 1.834e+00 2.038e-01 Crest Ckidney Cplasma Atubules Ametabolized AUC [1,] 0.000000 0.0000 0.000e+00 0.0000000 0.000e+00 0.0000000 [2,] 0.000000 0.0000 7.060e-07 0.0000000 5.000e-09 0.0000000 [3,] 0.008015 0.3847 4.590e-02 0.0005859 3.316e-03 0.0001704 [4,] 0.056450 1.7590 1.292e-01 0.0042390 1.856e-02 0.0010780 [5,] 0.150100 3.2970 2.041e-01 0.0116100 4.541e-02 0.0028280 [6,] 0.276300 4.5580 2.606e-01 0.0220600 8.041e-02 0.0052650 Warning messages: 1: In get_clint(dtxsid = dtxsid, chem.name = chem.name, chem.cas = chem.cas, : Clint is provided as a distribution. 2: In apply_clint_adjustment(Clint.point, Fu_hep = Fu_hep, suppress.messages = suppress.messages) : Clint adjusted for in vitro partitioning (Kilford, 2008), see calc_hep_fu. 3: In get_fup(dtxsid = dtxsid, chem.name = chem.name, chem.cas = chem.cas, : Fraction unbound is provided as a distribution. 4: In apply_fup_adjustment(fup.point, fup.correction = fup.adjustment, : Fup adjusted for in vivo lipid partitioning (Pearce, 2017), see calc_fup_correction. 5: In available_rblood2plasma(chem.cas = chem.cas, species = species, : Human in vivo measured Rblood2plasma used. 6: In get_caco2(chem.cas = chem.cas, chem.name = chem.name, dtxsid = dtxsid, : Default value of 1.6 used for Caco2 permeability. 7: In solve_model(chem.name = chem.name, chem.cas = chem.cas, dtxsid = dtxsid, : Rblood2plasma not recalculated. Set recalc.blood2plasma to TRUE if desired. 8: In solve_model(chem.name = chem.name, chem.cas = chem.cas, dtxsid = dtxsid, : Clearance not recalculated. Set recalc.clearance to TRUE if desired. > > p <- parameterize_pbtk(chem.name="Aminopterin")[sort(names(parameterize_pbtk(chem.name="Aminopterin")))] There were 16 warnings (use warnings() to see them) > for (this.param in order(sort(tolower(names(p))))) cat(paste(names(p)[this.param],": ",p[[this.param]],"\n")) BW : 70 Caco2.Pab : 1.6 Caco2.Pab.dist : NA Clint : 0 Clint.dist : NA Clmetabolismc : 0 Fabsgut : 0.6448 Fhep.assay.correction : 0.9561 Funbound.plasma : 0.747 Funbound.plasma.adjustment : 0.996 Funbound.plasma.dist : NA Kgut2pu : 1.68 Kkidney2pu : 3.569 Kliver2pu : 3.803 Klung2pu : 1.229 Krbc2pu : 0.8576 Krest2pu : 0.9694 MA : 19 MW : 440.4 Pow : 0.8903 Qcardiacc : 13.88 Qgfrc : 0.3099 Qgutf : 0.2054 Qkidneyf : 0.2214 Qliverf : 0.0535 Rblood2plasma : 0.8419 Vartc : 0.03827 Vgutc : 0.0158 Vkidneyc : 0.00419 Vliverc : 0.02448 Vlungc : 0.007235 Vrestc : 0.7765 Vvenc : 0.03827 hematocrit : 0.44 kgutabs : 0.3711 liver.density : 1.05 million.cells.per.gliver : 110 pKa_Accept : 8.09 pKa_Donor : 2.81 > > quit("no") > proc.time() user system elapsed 15.31 0.40 15.71